Breast-conserving surgery, or lumpectomy, is the most common surgical procedure for patients diagnosed with an early stage of invasive breast cancer. Clearly defined tumor margins and complete surgical removal of tumors are critical for preventing local recurrence and increasing disease-free survival. Currently, there is no accurate method to identify tumor margins pre- or intra-operatively. About 20% to 30% of the patients who undergo lumpectomy require additional surgery to excise any remaining tumors due to the presence of positive tumor margins. To develop a sensitive approach for detecting tumor margins in breast tissues, we propose to engineer a tumor targeted nanoparticle imaging probe and to realize the intraoperative imaging using microelectromechanical systems (MEMS) based photoacoustic tomography (PAT). The objectives of this proposed study are: 1) To develop a MEMS based dual-frequency photoacoustic tomography system for intraoperative tumor imaging; 2) To validate and optimize the nanoprobe-MEMS-PAT system using phantom and in vivo experiments; and 3) To evaluate the efficacy of in vivo nanoprobe-MEMS-PAT guided resection of mouse mammary tumors. The development of a sensitive and high resolution miniaturized MEMS based intraoperative photoacoustic imaging system should have great potential for determining tumor margins during surgery, preventing tumor recurrence and therefore, increasing the survival rate of breast cancer patients. PUBLIC HEALTH RELEVANCE: The objective of this proposed study is to develop a novel photoacoustic imaging approach that combines tumor targeted optical imaging probes with advanced microelectromechanical systems (MEMS) based photoacoustic imaging instrumentation for the detection of breast cancer and for outlining the tumor border during breast conserving surgery. In this study, we will use urokinase plasminogen activator receptor (uPAR) targeted near infrared (NIR) dye-labeled nanoparticles to deliver the imaging probes into breast tumors. The location and depth of the tumors will be detected using photoacoustic tomography. Success in this proposed study should provide us with a novel photoacoustic imaging instrument to address the urgent need for preventing tumor recurrence after breast conserving surgery and ultimately, to improve the survival rate of breast cancer patients.